Location of insulin receptors in the placenta and its progenitor tissues.

The insulin receptor gene is constitutively expressed, so the presence of insulin receptor proteins might be expected on all mammalian tissues, with the plasma membrane as the predominant site of receptor location. Results reviewed here indicate that insulin receptors are also present in all placental tissues and the placenta's progenitor tissues and cells, i.e., oocytes, spermatozoa, and preimplantation embryos, in most of the species studied. Receptor densities, however, vary among individual cells and cell types and at various developmental stages. Three aspects deserve emphasis. 1) In human placenta, the insulin receptor distribution pattern is characterized by a spatiotemporal change between first trimester and term. At the beginning of pregnancy, insulin receptors are found predominantly on the maternal side (apical membrane of syncytiotrophoblast, low density on cytotrophoblast); at term, however, they are on the fetal side (lining the fetal vessels). This suggests that, in the first trimester, maternal insulin regulates insulin-dependent processes, whereas, at term, it must be fetal insulin mainly controlling these processes. 2) The majority of insulin receptors is expressed on structures that are currently assumed to drive placental growth, i.e., syncytial sprouts and mesenchymal villi in first-trimester placentas and fetal endothelium at term. Therefore, we hypothesize a growth-promoting function, among others, of insulin on the placenta. 3) At present, no histologic evidence is available to demonstrate insulin receptors in structures commonly associated with receptor-mediated endocytosis. Whether placental insulin receptors are internalized, therefore, awaits clarification.